Discrimination between dopamine (DA) and norepinephrine (NE) is of considerable interest in modern methods of monitoring neurotransmission. It is proposed that RNA/DNA aptamers may be employed to bind DA or NE with high specificity and sensitivity. This binding interaction would be the basis for an optical or electrochemical based sensing scheme for distinguishing between the two neurotransmitters in biological samples. RNA and DNA aptamers have been shown to bind small molecule ligands with considerable strength and specificity and there has some success with incorporating them into sensor design. This project will start with thermodynamic characterization of a model RNA aptamer that binds the dye malachite green. These thermodynamic criteria for specific binding will then applied to the selection of aptamer candidates for binding DA over NE and/or NE over DA. The long-term goal of the project would be to incorporate the aptameric structures into an in vivo or in vitro biosensor. Such a sensing method would be of great benefit to in vivo studies of diseases and disorders of the central nervous system.